Cellular and Extracellular Adaptations of the Temporomandibular Joint Disk Epidemiological studies show that a large proportion of the population has alterations in joint anatomy, disk shape and position without having TMD. Furthermore, patients reporting signs of TMD, particularly pain, do no consistently have clinically observable alterations in form of the TMJ structures. One of the most significant obstacles to a clear understanding of mechanisms of TMD pathology is that there are not adequate models available and few attempts have been made to incorporate the epidemiological data an histologic findings into a model of the initiation and progression of TMD. The major aim of the following work is to characterize an animal model for temporomandibular dysfunction in humans, and to test possible mechanisms of initiation and progression in an appropriate cell culture system. The following three objectives are proposed: 1.Evaluate histology and immunohistochemistry of the temporomandibular joint in young versus aged baboons, in male versus female baboons, and in normal versus pathological joints. Much of the current literature suggests that naturally occurring TMD is unique to man and this attitude has impeded establishment of suitable animal models for experimental studies. Previous investigations have characterized the distribution of the major extracellular matrix (ECM) components in rabbit and rodent systems, but it is difficult to interpret their significance for human disease because of differences in both from and function between rodents and humans. 2.Evaluate the relative contributions of matrix hydration, fixed charge density and ion content to resistance to compressive load in the articular disk. The function of the fibrocartilage is dependent upon the intrinsic properties and organization of the major components of the disk. The organization of collagen provides resistance to tensile and stretching forces. Proteoglycans are thought to provide resistance to compressive load and control matrix hydration forming highly charged and hydrated complexes within the ECM. It is hypothesized that the ability of the ECM of the articular disk to resist compressive loads is due to increased levels of sulfation of the glycsaminoglycans, providing an increased density of fixed negative charges that alters the hydration properties of the disk and slows the motional properties of water organized around the fixed negative charges. 3.Evaluate changes in cytoskeletal architecture and integrin profiles in response to hydrostatic pressure and substance P in MG- 63 osteosarcoma cells. Integrins act as receptors for organized ECM components and interact with cytoskeletal components of the cell cytoplasm. Integrins have been shown to be active in transduction of mechanical forces and responsive to inflammatory mediators such al IL 1b. It is thought that mechanical forces initiate remodeling in pressure responsive tissues due to increased hydrostatic pressure, displacement of extracellular fluids, distortion of matrix and cells, translocation of ions and molecules, and stress-generated streaming potentials that interact with cell surface charges. The remodeling response can then be maintained or modified by chemical factors such as substance P and cytokines. It is hypothesized that the matrix-integrin- cytoskeletal linkages are responsive to both physical signals resulting from increased hydrostatic pressure and chemical signals such as Substance P that are released as a result of mechanical stimulation.